Implications of the accumulation of CXCR5+ NK cells in lymph nodes of HIV-1 infected patients.

BACKGROUND: B cell follicles are immune-privileged sites where intensive HIV-1 replication and latency occur, preventing a permanent cure. Recent study showed that CXCR5+ NK cells in B cell follicles can inhibit SIV replication in African green monkeys, but this has not been reported in HIV-1 infected patients. METHODS: Lymphocytes and tissue sections of lymph node were collected from 11 HIV-1 positive antiretroviral therapy (ART)-naive and 19 HIV-1 negative donors. We performed immunofluorescence and RNA-scope to detect the location of CXCR5+ NK cells and its relationship with HIV-1 RNA, and performed flow cytometry and RNA-seq to analyze the frequency, phenotypic and functional characteristics of CXCR5+ NK cells. The CXCL13 expression were detected by immunohistochemistry. FINDINGS: CXCR5+ NK cells, which accumulated in LNs from HIV-1 infected individuals, expressed high levels of activating receptors such as NKG2D and NKp44. CXCR5+ NK cells had upregulated expression of CD107a and ß-chemokines, which were partially impaired in HIV-1 infection. Importantly, the frequency of CXCR5+NK cells was inversely related to the HIV-1 viral burden in LNs. In addition, CXCL13-the ligand of CXCR5-was upregulated in HIV-1 infected individuals and positively correlated with the frequency of CXCR5+ NK cells. INTERPRETATION: During chronic HIV-1 infection, CXCR5+ NK cells accumulated in lymph node, exhibit altered immune characteristics and underlying anti-HIV-1 effect, which may be an effective target for a functional cure of HIV-1.

NDGA-P21, a novel derivative of nordihydroguaiaretic acid, inhibits glioma cell proliferation and stemness.

Nordihydroguaiaretic acid (NDGA) and its synthetic chiral analog dl-nordihydroguaiaretic acid (Nordy) show collective benefits in anti-tumor, and defending against viral and bacterial infections. Here, we synthetized a new derivative-NDGA-P21 based on NDGA structure. Regardless of the structural similarity, NDGA-P21 exhibited stronger capability in suppression of glioblastoma (GBM) cell growth as compared to Nordy. Mechanically, NDGA-P21 is able to arrest cell cycle of GBM cells in G0/G1 phase, and to block cell proliferation sequentially. It is important to note that NDGA-P21 is able to impair the stemness of glioma stem-like cells (GSLCs) via measurement of colony formation and sphere formation. Taken together, the novel NDGA-based compound NDGA-P21 exhibits potential therty -20 apeutic implications through inhibiting proliferation of glioma cells and self-renewal capability of GSLCs.